1. Field of the Invention
This invention is directed to novel organic compounds and is more specifically concerned with triazolo[4,3-a][1,5]benzodiazepines of the formulae IIIA and IIIB below and methods of the production thereof.
The novel compounds and the processes therefor can be illustratively represented as follows: ##STR8## wherein W is alkyl of 1 to 3 carbon atoms, inclusive, --CH.sub.2 Cl, or --CH.sub.2 OH; wherein R.sub.1 is hydrogen or methyl; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl defined as above, halogen, nitro, trifluoromethyl, and alkylthio in which alkyl is defined as above.
In addition the processes can be performed in a single step from a compound IA with an acid hydrazide or carbazate to give the compounds IIIA' and IIIB' respectively. If a compound IIIA is wanted with hydrogen in the 1-position, (R.sub.o is hydrogen) a compound of formula IA is reacted with triethyl orthoformate.
Further, treatment of a compound of formula IIIA (R.sub.o is hydrogen) ##STR9## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are defined as above, with chloro or bromosuccinimide gives the corresponding 1-chloro- or 1-bromo derivative of the above compound of formula III which can be converted to other derivatives of formula IIIA as described further on.
The compounds generically embraced by this invention are compounds IIIA and IIIB ##STR10## wherein R.sub.o is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, hydroxy, hydroxymethyl, and ##STR11## in which R" and R'" is selected from the group consisting of hydrogen and alkyl defined as above, or together ##STR12## is pyrrolidino, piperidino, morpholino, and N-methylpiperazino; wherein R is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, and ##STR13## in which R", R'" and ##STR14## are defined as above, wherein R.sub.1 is hydrogen or methyl; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl defined as above, halogen, nitro, trifluoromethyl, and alkylthio in which alkyl is defined as above, and the pharmacologically acceptable acid addition salts thereof.
The more desirable products are of the formulae ##STR15## wherein R.sub.o is selected from the group consisting of alkyl of 1 to 3 carbon atoms, inclusive, hydroxymethyl, and ##STR16## in which R" and R'" are hydrogen or alkyl defined as above; wherein R is selected from the group consisting of hydrogen, methyl or ##STR17## in which ##STR18## is defined as above; and wherein R.sub.2 and R.sub.4 are selected from the group consisting of hydrogen, chlorine, fluorine, bromine, --CF.sub.3 and nitro, and the pharmacologically acceptable acid addition salts thereof.
The most desirable products have the formulae: ##STR19## wherein R" and R'" are selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms, inclusive; and wherein R.sub.2 and R.sub.4 are selected from the group consisting of hydrogen and chlorine.
The process of this invention comprises: treating a compound of formula IA with hydrazine to hydrazine hydrate in methanol or ethanol to give the corresponding compound of formula IIA; treating IIA with a chloroacyl of the formula ##STR20## wherein W is alkyl of 1 to 3 carbon atoms --CH.sub.2 OH or --CH.sub.2 Cl; to give the corresponding compound of formula IIB which is cyclized by applying heat to give IIIA'.
If a compound IIIA is desired in which R.sub.o is hydrogen the step IIA.fwdarw.IIB is generally performed with triethylorthoformate.
The reaction from IA to IIIA' can also be performed in one step by reacting compound IA with a selected hydrazide of the formula ##STR21## wherein W is defined as above, in a higher boiling alcohol, e.g., n-butanol, n-hexanol, n-octanol, or the like, at a temperature between 115.degree. to the reflux temperature of the reaction mixture.
The triazolone compounds IIIB' are usually synthesized by reacting a compound of formula IA with a carbazate of the formula ##STR22## to obtain the compound of formula IIC; heating IIC to 200.degree.-250.degree. to obtain the compound of formula IIIB'.
Additional conventional procedures disclosed in this specification are used to produce other compounds under the general formulae IIIA and IIIB.